Venetoclax Combined with Hypomethylating Agents for Treatment-Naïve B/Myeloid Mixed Phenotype Acute Leukemia

Wu, Di; Chen, Wenlan; Chen, Zhichao; Li, Qiubai

doi:10.1155/2021/6661109

Cited by 10 publications

(17 citation statements)

References 21 publications

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“…In one study, two treatment-naïve patients were treated with a combination of a hypomethylating agent and the B-cell lymphoma-2 (BCL-2) inhibitor, venetoclax. Both patients subsequently received ASCT after achieving CR [ 15 ]. Additionally, blinatumomab, a bi-specific T-cell engager (BiTE) monoclonal antibody directed against CD19 was used to treat a patient whose performance status declined while being treated with hyper-CVAD.…”

Section: Discussionmentioning

confidence: 99%

Gilteritinib Combined with Azacitidine as Salvage Therapy for B/Myeloid Mixed Phenotype Acute Leukemia

Horvat¹,

Logothetis²,

Zhang³

et al. 2022

Cureus

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Mixed phenotype acute leukemia (MPAL) is a rare group of acute leukemias with blasts that co-express antigens of more than one lineage or separate populations of blasts of different lineages. Though treatment guidelines are not well established, the standard of care in treating MPAL remains the acute lymphoblastic leukemia (ALL)-derived chemotherapeutic regimen of hyper-cyclophosphamide, vincristine, doxorubicin (also known by its trade name, Adriamycin), and dexamethasone (CVAD) followed by allogeneic stem-cell transplant (ASCT). Beyond induction chemotherapy, evidence-based treatments remain to be investigated, especially regarding patients who relapse prior to ASCT. This case report illustrates a patient with relapsed MPAL following induction hyper-CVAD who was not immediately eligible for ASCT. After brief treatment with gilteritinib alone, the patient was started on gilteritinib and azacitidine as salvage therapy and achieved and maintained complete remission with incomplete count recovery (CRi) for eight months. Targeted therapy is a novel approach to improve survival rate, but unfortunately, there have been very few studies in the context of MPAL. We report a patient with relapsed FLT3-mutant MPAL who achieved remission using a combination approach with targeted therapy.

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Section: Discussionmentioning

confidence: 99%

Gilteritinib Combined with Azacitidine as Salvage Therapy for B/Myeloid Mixed Phenotype Acute Leukemia

Horvat¹,

Logothetis²,

Zhang³

et al. 2022

Cureus

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show abstract

“…Klocke et al [ 32 ] reported the case of a 65-year-old man with a complicated story of recurring relapses, ultimately controlled by the administration of venetoclax and decitabine, allowing to perform a second Allo-HSCT that led to more than 1 year of sustained CR at the time of publication. Finally, two patients with bi-lineal MPAL successfully received Allo-HSCT after chemotherapy lines of treatment including venetoclax and remain in CR several months later [ 33 ].…”

Section: Treatment Of Mpalmentioning

confidence: 99%

Mixed Phenotype/Lineage Leukemia: Has Anything Changed for 2021 on Diagnosis, Classification, and Treatment?

Béné

Porwit

2022

Curr Oncol Rep

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Purpose of Review Recent advances in the small field of the rare mixed phenotype acute leukemias (MPAL) are presented focusing on a better understanding of their pathophysiology and search for better therapeutic approaches. Recent Findings Three aspects of respective classification, therapy, and immunophenotype of MPAL are reviewed. New proposals have been made to segregate MPAL subtypes based on their genomic landscape. In parallel, it was found that a large array of therapeutic approaches has been tested in the past few years with increasingly good results. Finally, we explored the use of unsupervised flow cytometry analysis to dissect subtle variations in markers expression to better characterize the variegating aspect of MPALs. Summary Genomic and immunophenotypic aspects more clearly link MPAL subtypes with bona fide acute myeloblastic of lymphoblastic leukemias. This is likely to impact therapeutic strategies, towards a better management and outcome.

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“…Pre-clinical and clinical research has been conducted in KMT2A -rearranged leukemia (particularly in infants) and has shown increased sensitivity to both FLT3 and RAS inhibition, which could be translated into MPAL patients harboring such mutations [ 67 , 68 , 69 ]. Novel agents such as BCL-2 inhibitor venetoclax, in combination with hypomethylating agents, have been used to induce remission in MPAL [ 70 , 71 , 72 ]. Given the unique biology of MPAL, engineering hematopoietic stem cells harboring altered transcription factor profiles could mimic a pre-clinical model and allow the expanded testing of novel target agents, using a precision-medicine approach.…”

Section: Novel Approachesmentioning

confidence: 99%

Pediatric Mixed-Phenotype Acute Leukemia: What’s New?

Batra

Ross

2021

Cancers

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Mixed-phenotype acute leukemias (MPAL) are rare in children and often lack consensus on optimal management. This review examines the current controversies and emerging paradigms in the management of pediatric MPAL. We examine risk stratification, outcomes of recent retrospective and prospective collaborative trials, and the role of transplantation and precision genomics, and outline emerging targets and concepts in this rare entity.

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Venetoclax Combined with Hypomethylating Agents for Treatment-Naïve B/Myeloid Mixed Phenotype Acute Leukemia

Cited by 10 publications

References 21 publications

Gilteritinib Combined with Azacitidine as Salvage Therapy for B/Myeloid Mixed Phenotype Acute Leukemia

Gilteritinib Combined with Azacitidine as Salvage Therapy for B/Myeloid Mixed Phenotype Acute Leukemia

Mixed Phenotype/Lineage Leukemia: Has Anything Changed for 2021 on Diagnosis, Classification, and Treatment?

Pediatric Mixed-Phenotype Acute Leukemia: What’s New?

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